MAdCAM-1 co-stimulation combined with retinoic acid and TGF-ß induces blood CD8+ T cells to adopt a gutCD101+ TRM phenotype.

Resident memory T cells (TRMs) help control local immune homeostasis and contribute to tissue-protective immune responses. The local cues that guide their differentiation and localization are poorly defined. We demonstrate that mucosal vascular addressin cell adhesion molecule 1, a ligand for the gut-homing receptor α4ß7 integrin, in the presence of retinoic acid and transforming growth factor-ß (TGF-ß) provides a co-stimulatory signal that induces blood cluster of differentiation (CD8+ T cells to adopt a TRM-like phenotype. These cells express CD103 (integrin αE) and CD69, the two major TRM cell-surface markers, along with CD101. They also express C-C motif chemokine receptors 5 (CCR5) , C-C motif chemokine receptors 9 (CCR9), and α4ß7, three receptors associated with gut homing. A subset also expresses E-cadherin, a ligand for αEß7. Fluorescent lifetime imaging indicated an αEß7 and E-cadherin cis interaction on the plasma membrane. This report advances our understanding of the signals that drive the differentiation of CD8+ T cells into resident memory T cells and provides a means to expand these cells in vitro, thereby affording an avenue to generate more effective tissue-specific immunotherapies.

Substance Use, Violence, and Sexual Risk Among Young Cis-Gender Women Placed at High-Risk for Human Immunodeficiency Virus Infection.

The substance use, violence, and AIDS (SAVA) syndemic framework is used to study risk for HIV/AIDS. As a secondary analysis from a large HIV/AIDS prevention study, we categorized participants into having from zero to three SAVA conditions based on the presence or absence of self-reported substance use in the past 4 months, history of lifetime sexual abuse, and intimate partner violence. We used Poisson regression models to examine the association between the number of SAVA conditions and sexual risk behavior. Among all participants (n = 195, median age, 20), 37.9%, 19.5%, and 6.7% reported occurrence of one, two, and all three SAVA conditions, respectively. We found that more than one SAVA condition experienced by women was significantly associated with having more than one sex partner (adjusted prevalence ratio [aPR] = 1.88; 95% confidence interval [CI] = 1.28, 2.76) and with substance use before sex (aPR = 1.61 95% CI = 1.06, 2.45).